Rhabdomyosarcoma xenotransplants in zebrafish embryos.

Rhabdomyosarcomas (RMS) are the most common pediatric soft tissue sarcomas. High-risk and metastatic disease continues to be associated with very poor prognosis. RMS model systems that faithfully recapitulate the human disease and provide rapid, cost-efficient estimates of antitumor efficacy of candidate drugs are needed to facilitate drug development and personalized medicine approaches. Here, we present a new zebrafish-based xenotransplant model allowing for rapid and easily accessible drug screening using low numbers of viable tumor cells and relatively small amounts of water-soluble chemicals. Under optimized temperature conditions, embryonal RMS xenografts were established in zebrafish embryos at 3 h postfertilization (hpf). In proof-of-principle experiments, chemotherapy drugs with established clinical anti-RMS efficacy (vincristine, dactinomycin) and the mitogen-activated protein kinase kinase inhibitor trametinib were shown to significantly reduce the cross-sectional area of the tumors by 120 hpf. RMS xenograft models in zebrafish embryos henceforth could serve as a valuable addition to cell culture and mammalian models of RMS and represent a rapid and cost-effective solution for preclinical candidate drug testing. © 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.

Citation

Jakob Siebert, Michaela Schneider, Daniela Reuter-Schmitt, Julia Würtemberger, Annette Neubüser, Wolfgang Driever, Simone Hettmer, Friedrich G Kapp. Rhabdomyosarcoma xenotransplants in zebrafish embryos. Pediatric blood & cancer. 2023 Jan;70(1):e30053

Mesh Tags

PMID: 36317680

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